Human Cortical Pyramidal Neurons: From Spines to Spikes via Models.
Human Cortical Pyramidal Neurons: From Spines to Spikes via Models.
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DOI：
10.3389/fncel.2018.00181
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发表时间：
2018
影响因子：
5.3
通讯作者：
Segev I
中科院分区：
文献类型：
--
作者：
Eyal G;Verhoog MB;Testa-Silva G;Deitcher Y;Benavides-Piccione R;DeFelipe J;de Kock CPJ;Mansvelder HD;Segev I
我们提出了来自人类新皮层的锥体细胞的详细模型，包括它们的兴奋性突触、树突棘、树突NMDA-和体细胞/轴突Na+尖峰的模型，这些模型为这些主要细胞的信号处理和计算能力提供了新的见解。6个人类第2层和第3层锥体细胞（HL2/L3 PCs）被建立模型，整合了来自人类颞叶皮层新鲜和死后组织的详细解剖和生理数据。该模型预测每个突触接触的AMPA-和nmda -电导特别大（分别为0.88和1.31 nS）， nmda -电导对电压的依赖性很大。这些估计是基于突触连接的HL2/L3对的细胞内记录，结合细胞外电流注射和突触阻滞剂的使用，并假设每个突触连接有五个接触。高分辨率重建HL2/L3树突棘的大型数据集提供了脊柱头部（12.7±4.6 mV）、脊柱基部（9.7±5.0 mV）和脊柱体（0.3±0.1 mV）的epsp和脊柱颈部阻力（50-80 MΩ）的估计值。通过匹配实验体细胞Na+尖峰的形状和放电模式，可以估计体细胞/轴突可兴奋膜离子通道的密度，预测产生体细胞Na+尖峰（50%的概率）需要134±28个同时激活的HL2/L3-HL2/L3突触。当20±10个兴奋性棘突突触同时被激活时，在模型中触发树突NMDA峰值。HL2/L3细胞的基底树突数量特别多，其末端有明显的电缆伸长，这意味着这些细胞可以独立地同时产生约25个nmda尖峰，而大鼠体感觉皮层的L2/3细胞只有约14个。这些多位点非线性信号，加上庞大的（约30,000个）兴奋性突触/细胞，使人类L2/L3 pc具有增强的计算能力。我们的研究提供了迄今为止最全面的人类神经元模型，展示了人类皮质神经元的生物物理和计算独特性。
We present detailed models of pyramidal cells from human neocortex, including models on their excitatory synapses, dendritic spines, dendritic NMDA- and somatic/axonal Na+ spikes that provided new insights into signal processing and computational capabilities of these principal cells. Six human layer 2 and layer 3 pyramidal cells (HL2/L3 PCs) were modeled, integrating detailed anatomical and physiological data from both fresh and postmortem tissues from human temporal cortex. The models predicted particularly large AMPA- and NMDA-conductances per synaptic contact (0.88 and 1.31 nS, respectively) and a steep dependence of the NMDA-conductance on voltage. These estimates were based on intracellular recordings from synaptically-connected HL2/L3 pairs, combined with extra-cellular current injections and use of synaptic blockers, and the assumption of five contacts per synaptic connection. A large dataset of high-resolution reconstructed HL2/L3 dendritic spines provided estimates for the EPSPs at the spine head (12.7 ± 4.6 mV), spine base (9.7 ± 5.0 mV), and soma (0.3 ± 0.1 mV), and for the spine neck resistance (50–80 MΩ). Matching the shape and firing pattern of experimental somatic Na+-spikes provided estimates for the density of the somatic/axonal excitable membrane ion channels, predicting that 134 ± 28 simultaneously activated HL2/L3-HL2/L3 synapses are required for generating (with 50% probability) a somatic Na+ spike. Dendritic NMDA spikes were triggered in the model when 20 ± 10 excitatory spinous synapses were simultaneously activated on individual dendritic branches. The particularly large number of basal dendrites in HL2/L3 PCs and the distinctive cable elongation of their terminals imply that ~25 NMDA-spikes could be generated independently and simultaneously in these cells, as compared to ~14 in L2/3 PCs from the rat somatosensory cortex. These multi-sites non-linear signals, together with the large (~30,000) excitatory synapses/cell, equip human L2/L3 PCs with enhanced computational capabilities. Our study provides the most comprehensive model of any human neuron to-date demonstrating the biophysical and computational distinctiveness of human cortical neurons.
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大脑复杂性和大小提出的解剖问题：潜在的解决方案。
影响因子：
2.9
作者：
DeFelipe J
通讯作者：
DeFelipe J
影响因子：
4.3
作者：
Angelino, Elaine;Brenner, Michael P.
通讯作者：
Brenner, Michael P.
DOI：
10.1023/a:1024134312173
发表时间：
2002-03-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
Benavides-Piccione, R;Ballesteros-Yáñez, I;Yuste, R
通讯作者：
Yuste, R
影响因子：
4.3
作者：
Farinella, Matteo;Ruedt, Daniel T.;Silver, R. Angus
通讯作者：
Silver, R. Angus
影响因子：
5.3
作者：
Eyal, Guy;Mansvelder, Huibert D.;Segev, Idan
通讯作者：
Segev, Idan